Petric-Howe, Marija;
Crerar, Hamish;
Neeves, Jacob;
Harley, Jasmine;
Tyzack, Giulia;
Klein, Pierre;
Ramos, Andres;
... Luisier, Raphaelle; + view all
(2022)
Physiological intron retaining transcripts in the cytoplasm abound during human motor neurogenesis.
Genome Research
10.1101/gr.276898.122.
(In press).
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Abstract
Intron retention (IR) is now recognized as a dominant splicing event during motor neuron (MN) development, however the role and regulation of intron-retaining transcripts (IRTs) localized to the cytoplasm remain particularly understudied. Here we show that IR is a physiological process that is spatiotemporally regulated during MN lineage restriction and that IRTs in the cytoplasm are detected in as many as 13% (n=2297) of the genes expressed during this process. We identify a major class of cytoplasmic IRTs, which are not associated with reduced expression of their own genes, but instead show a high capacity for RNA-binding protein and miRNA occupancy. Finally, we show that ALS-causing VCP mutations lead to a selective increase in cytoplasmic abundance of this particular class of IRTs, which in turn temporally coincides with an increase in the nuclear expression level of predicted miRNA target genes. Altogether, our study identifies a previously unrecognized class of cytoplasmic intronic sequences with potential regulatory function beyond gene expression.
| Type: | Article |
|---|---|
| Title: | Physiological intron retaining transcripts in the cytoplasm abound during human motor neurogenesis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1101/gr.276898.122 |
| Publisher version: | https://doi.org/10.1101/gr.276898.122 |
| Language: | English |
| Additional information: | This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International license), as described at http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Cytoplasmic intron retention, human stem cell model, amyotrophic lateral sclerosis, miRNA |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10156780 |
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